Three-finger toxins(TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the Elapidae snake family, their presence has also been dete...Three-finger toxins(TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the Elapidae snake family, their presence has also been detected in the venoms of snakes from other families. The first TFT, α-bungarotoxin, was discovered almost 50 years ago and has since been used widely as a specific marker of the α7 and muscle-type nicotinic acetylcholine receptors. To date, the number of TFT amino acid sequences deposited in the UniProt Knowledgebase free-access database is more than 700, and new members are being added constantly.Although structural variations among the TFTs are not numerous, several new structures have been discovered recently; these include the disulfide-bound dimers of TFTs and toxins with nonstandard pairing of disulfide bonds. New types of biological activities have also been demonstrated for the well-known TFTs, and research on this topic has become a hot topic of TFT studies. The classic TFTs α-bungarotoxin and α-cobratoxin, for example, have now been shown to inhibit ionotropic receptors of γ-aminobutyric acid, and some muscarinic toxins have been shown to interact with adrenoceptors. New, unexpected activities have been demonstrated for some TFTs as well, such as toxin interaction with interleukin or insulin receptors and even TFT-activated motility of sperm. This minireview provides a summarization of the data that has emerged in the last decade on the TFTs and their activities.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of nat...Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of natural toxins present in the environment.Thus,there is growing concern about the potential detrimental effects that natural toxins could pose to achieve One Health.Interestingly,alkaloids,steroids and bioactive peptides obtained from natural toxins could be used for the development of therapeutic agents.Methodology:Our literature search focused on the following keywords;toxins,One Health,microbial toxins,mycotoxins,phytotoxins,phycotoxins,insect toxins and toxin effects.Google Scholar,Science Direct,PubMed and Web of Science were the search engines used to obtain primary databases.We chose relevant full-text articles and review papers published in English language only.The research was done between July 2022 and January 2023.Results:Natural toxins are poisonous substances comprising bioactive compounds produced by microorganisms,invertebrates,plants and animals.These compounds possess diverse structures and differ in biological function and toxicity,posing risks to human and animal health through the contamination of the environment,causing disease or death in certain cases.Findings from the articles reviewed revealed that effects of natural toxins on animals and humans gained more attention than the impact of natural toxins on the environment and lower organisms,irrespective of the significant roles that lower organisms play to maintain ecosystem balance.Also,systematic approaches for toxin control in the environment and utilization for beneficial purposes are inadequate in many regions.Remarkably,bioactive compounds present in natural toxins have potential for the development of therapeutic agents.These findings suggest that global,comprehensive and coordinated efforts are required for improved management of natural toxins through an interdisciplinary,One Health approach.Conclusion:Adopting a One Health approach is critical to addressing the effects of natural toxins on the health of humans,animals and the environment.展开更多
In this paper we highlight how the apparent double coverage of toxins and bioregulators by both the Biological and Toxin Weapons Convention(BTWC)and the Chemical Weapons Convention(CWC)in fact masks a regulatory gap t...In this paper we highlight how the apparent double coverage of toxins and bioregulators by both the Biological and Toxin Weapons Convention(BTWC)and the Chemical Weapons Convention(CWC)in fact masks a regulatory gap that has left such potentially dangerous agents neglected by both the control regimes during a period of rapid advances in relevant chemical,life and associated sciences and technologies.We first review what toxins,bioregulators and other mid-spectrum agents are and why they are of such concern and then examine how they are regulated under the BTWC and CWC.This paper then examines an illustrative range of contemporary chemical and life science research and associated activities of concern drawn from case study research on China,India,Iran,Russia,Syria and the United States,and assesses how the CWC and BTWC States Parties have inadequately addressed these threats.We then examine how both the CWC and BTWC Review Conferences failed to address these long-term challenges,and we end by providing a series of recommendations for how both regimes can be strengthened in this area.展开更多
Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and...Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.展开更多
Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^...Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.展开更多
Chronic hepatitis B causes a liver disease characterized by inflammation of the liver parenchyma. The aim of this study was to investigate the evolution of biological parameters in patients treated with Tenofovir for ...Chronic hepatitis B causes a liver disease characterized by inflammation of the liver parenchyma. The aim of this study was to investigate the evolution of biological parameters in patients treated with Tenofovir for chronic B infection at the Commune V referral health center in Bamako. We obtained a prevalence of 14.15%. The most represented age group was 31 - 40 years, with 36.8%. The sex ratio was 1.44 in favour of men. Viral load was undetectable after 18 months of treatment in 25 patients (42.37%). Tenofovir, the 1st-line drug in Mali, is effective on the biological parameters monitored in patients.展开更多
The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it...The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it has been reported that these are sensitive to the environmental conditions. For this reason, biopesticides products have been formulated based on secondary metabolites, recently. These biomolecules participate as biological control agent, such as: cyclic depsipeptides, amino acids, polyketides, polyphenols and terpenoids, affecting their morphology, life cycle and insect behavior. The use of secondary metabolites of entomopathogenic fungi opens the possibility of application in a more efficient way for the control of agricultural pests in a compatible with the environment and human health;therefore, it is important to know, analyzing the type of molecules, their effects, and their different methods of application.展开更多
Chemical insecticides have been considered as a means to combat crop pests. Although their effectiveness is evident, their impact on the environment is increasingly being discussed. The aim of this study is to determi...Chemical insecticides have been considered as a means to combat crop pests. Although their effectiveness is evident, their impact on the environment is increasingly being discussed. The aim of this study is to determine the agro-ecological potential of a biological insecticide (C<sub>25</sub>H<sub>32</sub>O<sub>12</sub>) based on Aloe barbadensis in a Sahelian context. For this purpose, a completely randomized block experimental design with 3 replications and 4 treatments was set up to experiment with Aloe barbadensis as a bioinsecticide against pests of Abelmoschus esculentus. However, data were collected using an observation and parameter monitoring grid. This includes the cultivation of Abelmoschus esculentus, soil preparation, seeding and watering, plot labeling, preparation of the bioinsecticide (selection and preparation of raw materials, grinding of Aloe barbadensis miller and extraction of the crude bioinsecticide, quantification of treatment doses and dilution, and obtaining the formulated bioinsecticide), plant watering, plant treatment, and finally parameter monitoring. The results obtained reveal that the level of damage is significantly high in the control treatment T0 (63%) compared to the other treatments, with 29% for treatment T1, 7% for T2, and 1% for T3, implying a strong action capability of this insecticide against pests of Abelmoschus esculentus. Therefore, it can be concluded that for a normal growing season of Abelmoschus esculentus, this biological insecticide should be sprayed 12 times. Furthermore, this biological insecticide is unique in that it does not inflict any gastric toxicity on the pests, which gives it the characteristic of being a repellent. It is a biological insecticide whose efficacy period has been tested, with a minimum duration of 21 days. In conclusion, this formulated bioinsecticide based on Aloe barbadensis demonstrates significant efficacy against pests of Abelmoschus esculentus. In the future, we will consider experimenting with its effectiveness against pests of other plants.展开更多
White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrien...White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of H.marmoreus mycelium.A series of changes occurred in H.marmoreus proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)technique.Some proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological stress.The proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and gluconeogenesis.The reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth retardation.This study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible fungi.It also provided a theoretical basis for protein function exploration and edible mushroom food safety research.展开更多
The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerativ...The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.展开更多
Millet (Pennisetum glaucum (L.) R. Br.) is the Sahelian crop par excellence due to its adaptation to the particular production conditions in this region. Unfortunately, in recent years this crop has been threatened by...Millet (Pennisetum glaucum (L.) R. Br.) is the Sahelian crop par excellence due to its adaptation to the particular production conditions in this region. Unfortunately, in recent years this crop has been threatened by very strong parasitic pressure and drought during the production period. The objective of this study is to analyze the main constraints of millet production and the solutions known to producers. A survey was carried out in November 2022 with a sample of 298 producers in five municipalities in the Tahoua region. The main constraints are drought and pressure from crop pests (locust, millet ear miner, floricultural insects) according to 57.9% of respondents. The millet ear miner is the most formidable pest according to 55% of respondents. Thus, the average yield obtained in a year of good production without the leafminer is 194 kg/ha and that obtained in a year of millet ear leafminer is around 27 kg to 43 kg/ha depending on the municipality. The yield obtained this last campaign after the attack of this leafminer varies from 64 to 77 kg/ha depending on the municipalities compared to a potential yield of over 1000 kg/ha. More than half of producers (58.1%) are unaware of the existence of biological control compared to only 12.5% who are aware of this alternative method. Work to popularize this technology is necessary in the five municipalities and the entire region in general.展开更多
One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing prom...One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.展开更多
Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also ...Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also effective in protecting the digestive system and preventing neurodegenerative diseases.In this review paper,we summarize the sources,structures and efficacies of the main active components in H.erinaceus fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular mechanisms.Based on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of H.erinaceus.Perspectives for future studies and new applications of H.erinaceus are proposed.展开更多
Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is a...Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is an indirect measure of the efficacy, safety, and tolerability of a drug. The objective of the study was to analyze the drug survival rate of biological therapy in a national health system (SUS). Methods: A retrospective cohort study of the medication process of RA was carried out in public pharmacies of a Brazilian state from January 2010 to April 2017. The Kaplan-Meier survival analysis was applied. The survival rate was defined as the incidence of drug discontinuation. The retention rate was defined as the mean of months using the drug. Results: Of the total of 902 individuals, 83.6% were female with a mean age of 56 years. Anti-TNF, mostly adalimumab (ADA), was the main biological agent prescribed. Mean drug retention of the first biological was 59.6 months (95% CI: 56.7 - 62.5), followed by 53.7 (95% CI: 48 - 59.4) and 28.2 (95% CI: 23.1 - 23.3) months for the second and third biologicals, respectively. Among the anti-TNF group, ADA, ETN, IFX had the better retention rate. There was no statistical difference in the general survival analyses (p = 0.18) among the groups. However, along the first 2 years, ADA, ETN, and RTX had the three better drug survival. The drug retention seems to increase with age (p = 0.036), with the subgroups > 70 years of age having the highest means (70 - 80 years: 67.29;>80: 67.53). Among all, 27.1% of patients switched to a second biologic. Conclusion: The anti-TNF group, mostly adalimumab (ADA), is the most prescribed medication as first and second-line therapy, reflecting its accessibility in the SUS and efficiency of the follow-up protocols. Among the anti-TNF group, ADA, ETN, and IFX had the better retention rate. Additionally, ADA and ETN had the better drug survival for the first treatment in the first 2 years. RTX was the non-anti-TNF with the best survival. A quarter of patients who start a biological therapy fail and switch to another drug (27%).展开更多
The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was...The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.展开更多
Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficie...Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.展开更多
Biological soil crusts(BSCs)play an important role in soil development and ecological function,and it is more important for quantitatively analyzing the processes and trends of BSCs to identify the advantages and disa...Biological soil crusts(BSCs)play an important role in soil development and ecological function,and it is more important for quantitatively analyzing the processes and trends of BSCs to identify the advantages and disadvantages of BSCs research for the development and application of BSCs theory.Bibliometric analysis of 2,186 BSCs literatures from Web of Science showed an exponential growth trend,as China and the United States as the top 2 in terms of publication volume.High quality publications are mainly from European and American countries,such as the United States,Germany and Spain.The top 3 publishers are Journal of Arid Environments,Soil Biology&Biochemistry and Plant and Soil,and disciplines include ecology,environmental science,and soil science,etc..Research institutions mainly affiliate to the Chinese Academy of Sciences,United States Department of the Interior,United States Geological Survey,Hebrew University of Jerusalem,Consejo Superior de Investigaciones Cientificas,and Universidad Rey Juan Carlos.Authors mainly come from United States,Israel,Spain and China.Funds are mainly from the National Natural Science Foundation of China,Spanish Government,Chinese Academy of Sciences,and National Science Foundation of the United States.Biological soil crusts(biocrusts,cyanobacteria,lichens,moss crusts,bryophytes),drylands,climate change,photosynthesis and desert are high-frequency keywords.Future research will focus on the driving mechanisms of BSCs on global biogeochemical cycles,maintaining global biodiversity on important ecological processes,global C,N,and P cycles.The impact on biological invasion,sandstorms,and water balance,multifunctional and reciprocal mechanisms for maintaining the stability of desert and sandy ecosystems,and impact on the formulation of management policies for arid ecosystems,corresponding to global climate change,and the estimation of regional,local,and microscale distribution of BSCs based on machine deep learning modeling gradually focus on.The ecosystem service functions of BSCs,the soil and water conservation and soil stability mediated by BSCs in arid and semi-arid regions,and the excavation of stress resistant genes for BSCs will be emphasized.展开更多
Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinic...Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.展开更多
Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD patt...Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.展开更多
基金Supported by The Russian Foundation for Basic Research,No.18-04-01075 and 18-54-00031
文摘Three-finger toxins(TFTs) comprise one of largest families of snake venom toxins. While they are principal to and the most toxic components of the venoms of the Elapidae snake family, their presence has also been detected in the venoms of snakes from other families. The first TFT, α-bungarotoxin, was discovered almost 50 years ago and has since been used widely as a specific marker of the α7 and muscle-type nicotinic acetylcholine receptors. To date, the number of TFT amino acid sequences deposited in the UniProt Knowledgebase free-access database is more than 700, and new members are being added constantly.Although structural variations among the TFTs are not numerous, several new structures have been discovered recently; these include the disulfide-bound dimers of TFTs and toxins with nonstandard pairing of disulfide bonds. New types of biological activities have also been demonstrated for the well-known TFTs, and research on this topic has become a hot topic of TFT studies. The classic TFTs α-bungarotoxin and α-cobratoxin, for example, have now been shown to inhibit ionotropic receptors of γ-aminobutyric acid, and some muscarinic toxins have been shown to interact with adrenoceptors. New, unexpected activities have been demonstrated for some TFTs as well, such as toxin interaction with interleukin or insulin receptors and even TFT-activated motility of sperm. This minireview provides a summarization of the data that has emerged in the last decade on the TFTs and their activities.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
基金supported by The Africa Education Initiative(NEF),USA and the National Veterinary Research Institute Vom,Nigeria.
文摘Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of natural toxins present in the environment.Thus,there is growing concern about the potential detrimental effects that natural toxins could pose to achieve One Health.Interestingly,alkaloids,steroids and bioactive peptides obtained from natural toxins could be used for the development of therapeutic agents.Methodology:Our literature search focused on the following keywords;toxins,One Health,microbial toxins,mycotoxins,phytotoxins,phycotoxins,insect toxins and toxin effects.Google Scholar,Science Direct,PubMed and Web of Science were the search engines used to obtain primary databases.We chose relevant full-text articles and review papers published in English language only.The research was done between July 2022 and January 2023.Results:Natural toxins are poisonous substances comprising bioactive compounds produced by microorganisms,invertebrates,plants and animals.These compounds possess diverse structures and differ in biological function and toxicity,posing risks to human and animal health through the contamination of the environment,causing disease or death in certain cases.Findings from the articles reviewed revealed that effects of natural toxins on animals and humans gained more attention than the impact of natural toxins on the environment and lower organisms,irrespective of the significant roles that lower organisms play to maintain ecosystem balance.Also,systematic approaches for toxin control in the environment and utilization for beneficial purposes are inadequate in many regions.Remarkably,bioactive compounds present in natural toxins have potential for the development of therapeutic agents.These findings suggest that global,comprehensive and coordinated efforts are required for improved management of natural toxins through an interdisciplinary,One Health approach.Conclusion:Adopting a One Health approach is critical to addressing the effects of natural toxins on the health of humans,animals and the environment.
基金supported by an Emeritus Fellowship from the Leverhulme Trust(EM-2018-005/10)to Professor Malcolm Dando.
文摘In this paper we highlight how the apparent double coverage of toxins and bioregulators by both the Biological and Toxin Weapons Convention(BTWC)and the Chemical Weapons Convention(CWC)in fact masks a regulatory gap that has left such potentially dangerous agents neglected by both the control regimes during a period of rapid advances in relevant chemical,life and associated sciences and technologies.We first review what toxins,bioregulators and other mid-spectrum agents are and why they are of such concern and then examine how they are regulated under the BTWC and CWC.This paper then examines an illustrative range of contemporary chemical and life science research and associated activities of concern drawn from case study research on China,India,Iran,Russia,Syria and the United States,and assesses how the CWC and BTWC States Parties have inadequately addressed these threats.We then examine how both the CWC and BTWC Review Conferences failed to address these long-term challenges,and we end by providing a series of recommendations for how both regimes can be strengthened in this area.
基金supported by Postdoctoral Innovation Talents’ Support Programthe National Natural Science Foundation of China (32130099)+1 种基金the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (TSBICIP-CXRC-038)Laboratory of Lingnan Modern Agriculture Project (NT2021005)。
文摘Valine is an essential amino acid and a type of branched-chain amino acid. Due to the involvement of branchedchain amino acids in various metabolic pathways, there has been a surge of interests in valine nutrition and its role in animal physiology. In pigs, the interactions between valine and other branched-chain amino acids or aromatic amino acids are complex. In this review, we delve into the interaction mechanism, metabolic pathways, and biological functions of valine. Appropriate valine supplementation not only enhances growth and reproductive performances, but also modulates gut microbiota and immune functions. Based on past observations and interpretations, we provide recommended feed levels of valine for weaned piglets, growing pigs, gilts, lactating sows, barrows and entire males. The summarized valine nutrient requirements for pigs at different stages offer valuable insights for future research and practical applications in animal husbandry.
基金supported by the National Natural Science Foundation of China,No.82173800 (to JB)Shenzhen Science and Technology Program,No.KQTD20200820113040070 (to JB)。
文摘Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.
文摘Chronic hepatitis B causes a liver disease characterized by inflammation of the liver parenchyma. The aim of this study was to investigate the evolution of biological parameters in patients treated with Tenofovir for chronic B infection at the Commune V referral health center in Bamako. We obtained a prevalence of 14.15%. The most represented age group was 31 - 40 years, with 36.8%. The sex ratio was 1.44 in favour of men. Viral load was undetectable after 18 months of treatment in 25 patients (42.37%). Tenofovir, the 1st-line drug in Mali, is effective on the biological parameters monitored in patients.
文摘The use of entomopathogenic fungi (EF) in recent years has been highly effective against the different orders of insects considered pests of agricultural importance and their conidia have been commonly applied, but it has been reported that these are sensitive to the environmental conditions. For this reason, biopesticides products have been formulated based on secondary metabolites, recently. These biomolecules participate as biological control agent, such as: cyclic depsipeptides, amino acids, polyketides, polyphenols and terpenoids, affecting their morphology, life cycle and insect behavior. The use of secondary metabolites of entomopathogenic fungi opens the possibility of application in a more efficient way for the control of agricultural pests in a compatible with the environment and human health;therefore, it is important to know, analyzing the type of molecules, their effects, and their different methods of application.
文摘Chemical insecticides have been considered as a means to combat crop pests. Although their effectiveness is evident, their impact on the environment is increasingly being discussed. The aim of this study is to determine the agro-ecological potential of a biological insecticide (C<sub>25</sub>H<sub>32</sub>O<sub>12</sub>) based on Aloe barbadensis in a Sahelian context. For this purpose, a completely randomized block experimental design with 3 replications and 4 treatments was set up to experiment with Aloe barbadensis as a bioinsecticide against pests of Abelmoschus esculentus. However, data were collected using an observation and parameter monitoring grid. This includes the cultivation of Abelmoschus esculentus, soil preparation, seeding and watering, plot labeling, preparation of the bioinsecticide (selection and preparation of raw materials, grinding of Aloe barbadensis miller and extraction of the crude bioinsecticide, quantification of treatment doses and dilution, and obtaining the formulated bioinsecticide), plant watering, plant treatment, and finally parameter monitoring. The results obtained reveal that the level of damage is significantly high in the control treatment T0 (63%) compared to the other treatments, with 29% for treatment T1, 7% for T2, and 1% for T3, implying a strong action capability of this insecticide against pests of Abelmoschus esculentus. Therefore, it can be concluded that for a normal growing season of Abelmoschus esculentus, this biological insecticide should be sprayed 12 times. Furthermore, this biological insecticide is unique in that it does not inflict any gastric toxicity on the pests, which gives it the characteristic of being a repellent. It is a biological insecticide whose efficacy period has been tested, with a minimum duration of 21 days. In conclusion, this formulated bioinsecticide based on Aloe barbadensis demonstrates significant efficacy against pests of Abelmoschus esculentus. In the future, we will consider experimenting with its effectiveness against pests of other plants.
基金funded by the Shandong Provincial Natural Science Foundation,China (ZR2020QC005)the National Natural Science Foundation of China (32272789)+3 种基金the National Natural Science Foundation of China (32000041)the Shandong Edible Fungus Agricultural Technology System (SDAIT-07-02)the Shandong Provincial Key Research and Development Plan (2021ZDSYS28)the Qingdao Agricultural University Scientific Research Foundation (6631120076)。
文摘White Hypsizygus marmoreus is a popular edible mushroom.Its mycelium is easy to be contaminated by Penicillium,which leads to a decrease in its quality and yield.Penicillium could compete for limited space and nutrients through rapid growth and produce a variety of harmful gases,such as benzene,aldehydes,phenols,etc.,to inhibit the growth of H.marmoreus mycelium.A series of changes occurred in H.marmoreus proteome after contamination when detected by the label-free tandem mass spectrometry(MS/MS)technique.Some proteins with up-regulated expression worked together to participate in some processes,such as the non-toxic transformation of harmful gases,glutathione metabolism,histone modification,nucleotide excision repair,clearing misfolded proteins,and synthesizing glutamine,which were mainly used in response to biological stress.The proteins with down-regulated expression are mainly related to the processes of ribosome function,protein processing,spliceosome,carbon metabolism,glycolysis,and gluconeogenesis.The reduction in the function of these proteins affected the production of the cell components,which might be an adjustment to adapt to growth retardation.This study further enhanced the understanding of the biological stress response and the growth restriction adaptation mechanisms in edible fungi.It also provided a theoretical basis for protein function exploration and edible mushroom food safety research.
文摘The search for new biomarkers predictive of type 2 diabetes currently constitutes a research avenue in Bioclinical. Total homocysteine remains a preferred target due to its involvement in the occurrence of degenerative complications in type 2 diabetics. The aim of this work was to study hyperhomocysteinemia and other biochemical markers associated with T2D in the Congolese population. This was an analytical case-control study carried out between October 2022 and October 2023. The study population consisted of 150 subjects including 100 T2D patients and 50 control subjects. The main clinical data were collected on a pre-established form. Homocysteine determination was carried out by the sandwich ELISA method. The other biochemical markers were measured by colorimetric enzymatic methods. Hyperhomocysteinemia was present in 27.3% (41/150) of the entire study population. Type 2 diabetics had a frequency of hyperhomocysteinemia of 36% (36/100) and control 10% (5/50) (p = 0.001). The mean hyperhomocysteinemia concentration was 31.9 μmol/l with extremes ranging from 18 to 103 μmol/l. Means of biological markers between diabetics and controls showed a statistically significant difference (p = 0.01). The risk factors associated with this HHcy were: sex (OR = 3.5), age (OR = 9.4), sedentary lifestyle (OR = 3.4) and glycosylated hemoglobin (OR = 12) with a p-value <0.05 respectively. Our results suggest that hyperhomocysteinemia can be considered as a predictive biomarker in the bioclinic of Congolese type 2 diabetic patients.
文摘Millet (Pennisetum glaucum (L.) R. Br.) is the Sahelian crop par excellence due to its adaptation to the particular production conditions in this region. Unfortunately, in recent years this crop has been threatened by very strong parasitic pressure and drought during the production period. The objective of this study is to analyze the main constraints of millet production and the solutions known to producers. A survey was carried out in November 2022 with a sample of 298 producers in five municipalities in the Tahoua region. The main constraints are drought and pressure from crop pests (locust, millet ear miner, floricultural insects) according to 57.9% of respondents. The millet ear miner is the most formidable pest according to 55% of respondents. Thus, the average yield obtained in a year of good production without the leafminer is 194 kg/ha and that obtained in a year of millet ear leafminer is around 27 kg to 43 kg/ha depending on the municipality. The yield obtained this last campaign after the attack of this leafminer varies from 64 to 77 kg/ha depending on the municipalities compared to a potential yield of over 1000 kg/ha. More than half of producers (58.1%) are unaware of the existence of biological control compared to only 12.5% who are aware of this alternative method. Work to popularize this technology is necessary in the five municipalities and the entire region in general.
文摘One of the main immune-mediated diseases that lead to avoidable blindness is non-infectious uveitis. Glucocorticoids are the first-line therapy choice for noninfectious uveitis;however, biologics are also showing promise in the management of this condition. The description of glucocorticoid and biologic usage in non-infectious uveitis is the main topic of this paper.
基金supported by the fund from Natural Science Foundation of Zhejiang Province,China(LY17C200017)。
文摘Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing immunity.It is also effective in protecting the digestive system and preventing neurodegenerative diseases.In this review paper,we summarize the sources,structures and efficacies of the main active components in H.erinaceus fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular mechanisms.Based on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of H.erinaceus.Perspectives for future studies and new applications of H.erinaceus are proposed.
文摘Background: Biological therapy prevents structural damage, improves functional capacity, and has provided an important advance in the treatment of rheumatoid arthritis (RA). In a real-life scenario, drug survival is an indirect measure of the efficacy, safety, and tolerability of a drug. The objective of the study was to analyze the drug survival rate of biological therapy in a national health system (SUS). Methods: A retrospective cohort study of the medication process of RA was carried out in public pharmacies of a Brazilian state from January 2010 to April 2017. The Kaplan-Meier survival analysis was applied. The survival rate was defined as the incidence of drug discontinuation. The retention rate was defined as the mean of months using the drug. Results: Of the total of 902 individuals, 83.6% were female with a mean age of 56 years. Anti-TNF, mostly adalimumab (ADA), was the main biological agent prescribed. Mean drug retention of the first biological was 59.6 months (95% CI: 56.7 - 62.5), followed by 53.7 (95% CI: 48 - 59.4) and 28.2 (95% CI: 23.1 - 23.3) months for the second and third biologicals, respectively. Among the anti-TNF group, ADA, ETN, IFX had the better retention rate. There was no statistical difference in the general survival analyses (p = 0.18) among the groups. However, along the first 2 years, ADA, ETN, and RTX had the three better drug survival. The drug retention seems to increase with age (p = 0.036), with the subgroups > 70 years of age having the highest means (70 - 80 years: 67.29;>80: 67.53). Among all, 27.1% of patients switched to a second biologic. Conclusion: The anti-TNF group, mostly adalimumab (ADA), is the most prescribed medication as first and second-line therapy, reflecting its accessibility in the SUS and efficiency of the follow-up protocols. Among the anti-TNF group, ADA, ETN, and IFX had the better retention rate. Additionally, ADA and ETN had the better drug survival for the first treatment in the first 2 years. RTX was the non-anti-TNF with the best survival. A quarter of patients who start a biological therapy fail and switch to another drug (27%).
基金Startup Fund for scientific research,Fujian Medical University,Grant/Award Number:2020QH1039Joint Funds for the Innovation of Science and Technology,Fujian Province,Grant/Award Number:2020Y9114 and 2020Y9119。
文摘The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.
基金supported by the National Natural Science Foundation of China(Grant Nos.32030099 and 32072670)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA28020301)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2023326)the Enterprise Cooperation Projects of China(Grant No.Am20210407RD).
文摘Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.
基金supported by the National Natural Science Foundation of China(No.32260292,32060277)National Key Research and Development Program of China(No.2020YFC1522200)+2 种基金Shanxi Provincial Basic Research Program of China(No.202303021212060)Shanxi Provincial Cultural Relics Technology Program of China(No.2023KT15)The Local Project Guided by the Central Government of Gansu Province(No.YDZX20216200001728).
文摘Biological soil crusts(BSCs)play an important role in soil development and ecological function,and it is more important for quantitatively analyzing the processes and trends of BSCs to identify the advantages and disadvantages of BSCs research for the development and application of BSCs theory.Bibliometric analysis of 2,186 BSCs literatures from Web of Science showed an exponential growth trend,as China and the United States as the top 2 in terms of publication volume.High quality publications are mainly from European and American countries,such as the United States,Germany and Spain.The top 3 publishers are Journal of Arid Environments,Soil Biology&Biochemistry and Plant and Soil,and disciplines include ecology,environmental science,and soil science,etc..Research institutions mainly affiliate to the Chinese Academy of Sciences,United States Department of the Interior,United States Geological Survey,Hebrew University of Jerusalem,Consejo Superior de Investigaciones Cientificas,and Universidad Rey Juan Carlos.Authors mainly come from United States,Israel,Spain and China.Funds are mainly from the National Natural Science Foundation of China,Spanish Government,Chinese Academy of Sciences,and National Science Foundation of the United States.Biological soil crusts(biocrusts,cyanobacteria,lichens,moss crusts,bryophytes),drylands,climate change,photosynthesis and desert are high-frequency keywords.Future research will focus on the driving mechanisms of BSCs on global biogeochemical cycles,maintaining global biodiversity on important ecological processes,global C,N,and P cycles.The impact on biological invasion,sandstorms,and water balance,multifunctional and reciprocal mechanisms for maintaining the stability of desert and sandy ecosystems,and impact on the formulation of management policies for arid ecosystems,corresponding to global climate change,and the estimation of regional,local,and microscale distribution of BSCs based on machine deep learning modeling gradually focus on.The ecosystem service functions of BSCs,the soil and water conservation and soil stability mediated by BSCs in arid and semi-arid regions,and the excavation of stress resistant genes for BSCs will be emphasized.
基金financially supported by the National Natural Science Foundation of China(grant no.8217070298)Guangdong Basic and Applied Basic Research Foundation(grant no.2020A1515110770,2021A1515220011,2022A1515010335).
文摘Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.
基金supported by the National Natural Science Foundation of China(32088101)National key Research and Development Program of China(2017YFC1700105,2021YFA1301603).
文摘Objective:To elucidate the biological basis of the heart qi deficiency(HQD)pattern,an in-depth understanding of which is essential for improving clinical herbal therapy.Methods: We predicted and characterized HQD pattern genes using the new strategy,TCM-HIN2Vec,which involves heterogeneous network embedding and transcriptomic experiments.First,a heterogeneous network of traditional Chinese medicine(TCM)patterns was constructed using public databases.Next,we predicted HQD pattern genes using a heterogeneous network-embedding algorithm.We then analyzed the functional characteristics of HQD pattern genes using gene enrichment analysis and examined gene expression levels using RNA-seq.Finally,we identified TCM herbs that demonstrated enriched interactions with HQD pattern genes via herbal enrichment analysis.Results: Our TCM-HIN2Vec strategy revealed that candidate genes associated with HQD pattern were significantly enriched in energy metabolism,signal transduction pathways,and immune processes.Moreover,we found that these candidate genes were significantly differentially expressed in the transcriptional profile of mice model with heart failure with a qi deficiency pattern.Furthermore,herbal enrichment analysis identified TCM herbs that demonstrated enriched interactions with the top 10 candidate genes and could potentially serve as drug candidates for treating HQD.Conclusion: Our results suggested that TCM-HIN2Vec is capable of not only accurately identifying HQD pattern genes,but also deciphering the basis of HQD pattern.Furthermore our finding indicated that TCM-HIN2Vec may be further expanded to develop other patterns,leading to a new approach aimed at elucidating general TCM patterns and developing precision medicine.